Newer Therapeutic Targets in Head and Neck Cancers

A Cohort Study to Identify Newer Therapeutic Targets in Head and Neck Cancers

Based on the recently identified mutations in HNSCCs, the major pathologic pathways implicated in the tumorigenesis of HNSCC include dysregulation of four processes:

1. cellular survival and proliferation (e.g., TP53, EGFR, MET, and PIK3CA);
2. cell-cycle control (e.g., CDKN2A and CCND1);
3. cellular differentiation (e.g., NOTCH1); and
4. Adhesion and invasion signaling (e.g., FAT1).7 TP53, EGFR, PIK3CA, CDKN2A, CCND1, and MET participate in several common signaling pathways.

Alterations of these genes are most frequently seen in alcohol and tobacco-related HNSCC. However their role in prognostication and selection of therapeutics is not known

Study Overview

• Status: Recruiting
• Conditions: Oral Cancer; Head Neck Cancer
• Intervention / Treatment: Other: Next generation Sequencing

Detailed Description

Sample size:

Patients with squamous cell carcinoma of oral cavity fulfilling the inclusion and exclusion criteria and willing to participate will be included in this study.

Method:

Comprehensive history and physical examination of the patients will be carried out and all the details will be recorded in the preset proforma. All routine investigations as indicated including a biopsy to establish a diagnosis and CT of the head and neck to measure the tumor dimensions and stage the disease before initiation of treatment will be recorded. The paraffin embedded tissue will be studied for expression of various genetic mutations using NGS platform. Brush cytology will be collected in liquid medium for HPV typing using PCR.

The Ion AmpliSeq™ Cancer Hotspot Panel v3 will be used to detect hotspot regions of 161 oncogenes and tumor suppressor genes This research panel, with improved primer design, contains 4,648 total 4 pools (DNA pool 1: 1,891 amplicons. DNA pool 2: 1,890 amplicons. RNA pool 1: 447 amplicons. RNA pool 2: 420 amplicons.), enabling researchers to sequence challenging samples of formalin-fixed, paraffin-embedded (FFPE) tissue. Copy Number Variants (CNVs), Gene Fusions, Insertions-Deletions (indels), Single Nucleotide Polymorphisms (SNPs), Somatic Variants are identified.

HPV DNA PCR METHODOLOGY

DNA will be isolated by using QIAamp DNA mini kit (Qiagen, Hilden, Germany). The presence of HPV will be detected by using the digene® HC2 HPV DNA Test- The digene HC2 HPV DNA Test uses Hybrid Capture 2 technology to detect high-risk and low-risk HPV genotypes. It uses in vitro microplate assay based on signal-amplified nucleic acid hybridization that uses chemiluminescence for the qualitative detection of 18 types of human papillomavirus (HPV) (13 high risk and 5 low risk) DNA in cervical specimens. The test uses an RNA probe cocktail that detects 13 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/68) and 5 low-risk types (6/11/42/43/44).

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Manoj Pandey, MS, PhD; Phone Number: 9336363640; Email: manojpandey66@gmail.com

Study Locations

• India
  • UP
    • Varanasi, UP, India, 221005
      • Recruiting
      • Banaras Hindu University
      • Contact: Keshav Murthy, MS; Phone Number: 9035424293; Email: keshav.murthy.bmcri@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Histologically proven cases of Head and neck cancer undergoing treatment will be included, Next generation sequencing will be done and cohort will be followed up for 10 years

Description

Inclusion Criteria:

• Histologically proven cases of primary head and neck cancers.

Exclusion Criteria:

• Patients under 18 years of age
• Pregnant and lactating women
• Multiple cancers or patients with cancer of other sites.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Head neck cancer; Histologically diagnosed cases of head and neck cancer	Other: Next generation Sequencing; Next generation sequencing for 161 genes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Over all survival	Survival time from the diagnosis to death	10 years
Relapse free survival	survival time from diagnosis to recurrence or metastasis	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	The time from the diagnosis to progression of disease	5 years

Collaborators and Investigators

• Sponsor: Banaras Hindu University
• Investigators: Principal Investigator: Manoj Pandey, MS, PhD, Professor

Publications and helpful links

General Publications

• Batta N, Pandey M. Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance. World J Surg Oncol. 2019 Nov 27;17(1):198. doi: 10.1186/s12957-019-1741-2.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: predictive biomarker; Next generation sequencing
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Stomatognathic Diseases; Mouth Diseases; Head and Neck Neoplasms; Mouth Neoplasms
• Other Study ID Numbers: NGSHN1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On request
• IPD Sharing Time Frame: 6 months
• IPD Sharing Access Criteria: On request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Mutation data
   Information comments: Data of 37 mutations identified till 2020 has been uploaded, more mutations will be uploaded soon

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No